As a therapeutic drug for gout and hyperuricemia, allopurinol having a xanthine oxidase inhibitory activity has been traditionally used. In addition, as compounds having a xanthine oxidase inhibitory activity, 2-phenylthiazole derivative (WO92/09279), 1-phenylpyrazole compound (WO98/18765), 3-phenylpyrazole compound (JP-A-10-310578) and the like have been reported.
It has been suggested that reactive oxygen species (ROS) is involved in pathologic symptoms of inflammation, ischemia-reperfusion injury, carcinogenesis, aging and the like (OYANAGI Yoshihiko: O2−/NO pharmacology (NIHON IGAKUKAN, 1997)). It has been further considered that xanthine oxidase (XO) is an in vivo source of ROS because it is an enzyme involved in uric acid synthesis in purine metabolism and is also involved in superoxide anion production (McCord J M: Oxygen-derived free radicals in postischemic tissue injury, N. Engl. J. Med., 312, 159–163 (1985)). Since allopurinol is known as an XO inhibitor, involvement of XO in the above-mentioned diseases has been conventionally studied using this compound. However, since allopurinol itself shows a radical removing (scavenging) effect (Moorhouse P C, Grootveld M, Halliwell B, Quinlan J G, Gutteridge J M: Allopurinol and oxipurinol are hydroxyl radical acavengers, FEBS Lett., 213, 23–28 (1987)), study of the relationship between XO and active oxygen has been difficult.
As an XO inhibitor much potent than allopurinol and free of radical scavenging effect, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (development code: Y-700) and the like have been recently reported and are currently under development as therapeutic drugs for gout and hyperuricemia.
However, a tumorigenesis suppressive effect, or how colon cancer is actually affected by the administration of an XO inhibitor or 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (hereinafter to be referred to as Y-700), which is one of the XO inhibitors, has not been clarified.